The proposed project will support 'translational medicine', defined as "a basic laboratory discovery that becomes applicable to the diagnosis, treatment or prevention of a specific disease". Our goal is to improve the probability of a laboratory discovery that impacts human health by providing a better research tool for studies using pigs. Pigs develop conditions similar to humans (diabetes, cardiovascular disease, hypertension, obesity) and are useful to researchers trying to identify both causes and treatments of these diseases. The anatomical similarities between the cardiovascular system of pigs and humans makes them a useful surrogate for testing new medical devices such as stents. Pig and human cytochrome P450 enzymes are so homologous that pigs should be the preferred model for drug metabolism and pharmacokinetics studies. Yet, pigs are under-utilized. A device that makes it easier to obtain their biofluids, and also simultaneously acquires physiological data from conscious and mobile subjects, could increase the value of pigs to human health research. The reduction of stress associated with elimination of restraints or handling, should also improve the quality of data by reducing hormones which confound the study (e.g. catecholamine release redirecting blood flow away from the liver, kidney and gastrointestinal tract during a pharmacokinetics study). Therefore, we propose to refine and expand the capabilities of a prototype movement-responsive cage that we built, and began to test, during Phase I studies. The project milestones outline the successive addition of capabilities to this cage, including automated blood sampling, programmed dosing, and physiological data acquisition modules for core body temperature, blood pressure and electrocardiography. In accordance with the intent of the SBIR program, the ultimate objective is an instrument that can be sold to laboratories involved in pharmaceutical and biomedical research. Each development milestone will culminate in validation experiments, to be accomplished by comparing data acquired using the new technique with data either from the literature or from a crossover study employing a conventional technique. For example, the concentration of the same drug will be compared in blood sampled manually from a restrained pig vs blood sampled automatically from a mobile pig. Another validation study will evaluate comparisons with human data. For example, one advantage of using a pig for pharmacokinetics studies is their acceptance of solid dosing forms, such as capsules or tablets. Pigs swallow pills willingly, without coercion or handling, if the pills are hidden in a cookie. This device will collect programmed blood samples to establish the pharmacokinetics of a solid dose, and provide comparisons of different formulations within the same subject. When successive doses represent a marketed or generic drug, the pig will provide drug bioequivalence data. Demonstration of the same level of oral bioavailability in the pig and human for marketed drugs would validate the technique, and encourage initial screening in pigs instead of relying solely on human clinical trials for bioequivalence. The pig is a valuable model for human illnesses such as diabetes, obesity, and cardiovascular disease. Simultaneous pharmacology studies in pigs will accelerate research by providing more relevant information to those scientists trying to characterize these health problems, and also to the pharmaceutical researchers trying to develop treatments. The movement-responsive cage facilitates simultaneous pharmacology studies. [unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]